Document Type

Article

Publication Date

1-1-2008

Publication Title

Steroids

Abstract

Previous studies have demonstrated that cyclooxygenase-2 (COX-2) inhibitor NS-398 decrease aromatase activity at the transcript level in breast cancer cells. However, N-Methyl NS-398, which does not have COX-2 inhibitory activity but has very similar structure to NS-398, decreases aromatase activity and transcription in MCF-7 and MDA-MB-231 breast cells to the same extent as NS-398. This suggests that NS-398 decrease aromatase expression in breast cancer cells via other mechanism(s). Further investigations find that both compounds only decrease aromatase activity stimulated by forskolin/phorbol ester at the transcript level in both breast cancer cell lines and in breast stromal cells from patients. They do not affect aromatase expression and activity stimulated by dexamethasone. Both compounds also suppress MCF-7 cell proliferation stimulated by testosterone. Aromatase inhibition studies using placental microsomes demonstrate that the compounds show only weak direct aromatase inhibition. These results suggest that NS-398 and its N-methyl analog suppress aromatase expression and activity with multiple mechanisms.

Comments

This work was supported by the National Institutes of Health (NIH) Grant R01 CA73698 (to R.W.B.), the NIH Chemistry and Biology Interface Training Program Grant T32 GM08512 (to E.S.D.-C.), and The Ohio State University Comprehensive Cancer Center Breast Cancer Research Fund.

DOI

10.1016/j.steroids.2007.09.011

Version

Postprint

Volume

73

Issue

1

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